1. Field of the Invention
The present invention relates to the field of medical procedures, particularly invasive medical procedures, and more particularly invasive medical procedures to the brain.
2. Background of the Art
The brain is found inside the bony covering called the cranium. The cranium protects the brain from injury. Together, the cranium and bones that protect our face are called the skull. Meninges are three layers of tissue that cover and protect the brain and spinal cord. From the outermost layer inward they are: the dura mater, arachnoid and pia mater. In the brain, the dura mater is made up of two layers of whitish, inelastic (not stretchy) film or membrane. The outer layer is called the periosteum. An inner layer, the dura, lines the inside of the entire skull and creates little folds or compartments in which parts of the brain are neatly protected and secured. There are two special folds of the dura in the brain, the falx and the tentorium. The falx separates the right and left half of the brain and the tentorium separates the upper and lower parts of the brain.
The second layer of the meninges is the arachnoid. This membrane is thin and delicate and covers the entire brain. There is a space between the dura and the arachnoid membranes that is called the subdural space. The arachnoid is made up of delicate, elastic tissue and blood vessels of different sizes. The layer of meninges closest to the surface of the brain is called the pia mater. The pia mater has many blood vessels that reach deep into the surface of the brain. The pia, which covers the entire surface of the brain, follows the folds of the brain. The major arteries supplying the brain provide the pia with its blood vessels. The space that separates the arachnoid and the pia is called the subarachnoid space. A clear fluid may often lie within the interface between the pia and the next adjacent layer.
Cerebrospinal fluid, also known as CSF, is found within the brain and surrounds the brain and the spinal cord. It is a clear, watery substance that helps to cushion the brain and spinal cord from injury. This fluid circulates through channels around the spinal cord and brain, constantly being absorbed and replenished. It is within hollow channels in the brain, called ventricles, where the fluid is produced. A specialized structure within each ventricle, called the choroid plexus, is responsible for the majority of CSF production. The brain normally maintains a balance between the amount of cerebrospinal fluid that is absorbed and the amount that is produced. Often, disruptions in the system occur.
Although various forms of interventional and drug therapy procedures have been performed on the brain since the time of the Pharaohs in Egypt, significant technical advances in procedures are essential to the improvement of success in such procedures. Even as drug delivery to regions of the brain by localized invasive procedures has become available, the procedures still need to be refined for different regions, different drugs, and new and effective methodologies of delivery become desirable.
The pia has been generally treated as a barrier or annoyance in accessing or treating areas of the brain during surgery and procedures have been generally performed without any attempt to use the presence of the pia as a benefit. See for example, the procedures in Journal of Neuroscience, Volume 16, Number 18, Issue of Sep. 15, 1996 pp. 5864-5869; Interaction of Perirhinal Cortex with the Fornix-Fimbria: Memory for Objects and ‘Object-in-Place’ Memory, David Gaffan and Amanda Parker.
U.S. Pat. Nos. 6,663,857; 6,506,378; 5,762,926 and 5,082,670 describe graft procedures wherein a graft may be placed in a ventricle, e.g. a cerebral ventricle or subdurally, i.e. on the surface of the host brain where it is separated from the host brain parenchyma by the intervening pia mater or arachnoid and pia mater. Grafting to the ventricle may be accomplished by injection of the producer cells or by growing the cells in a substrate such as 30% collagen to form a plug of solid tissue which may then be implanted into the ventricle to prevent dislocation of the graft. For subdural grafting, the cells may be injected around the surface of the brain after making a slit in the dura. Injections into selected regions of the host brain may be made by drilling a hole and piercing the dura to permit the needle of a microsyringe to be inserted. The microsyringe is preferably mounted in a stereotaxic frame and three dimensional stereotaxic coordinates are selected for placing the needle into the desired location of the brain.
U.S. Pat. No. 5,843,048 (Gross) describes syringe tip designs for use in epidural applications. The designs include straight epidural needles employed in the former procedure do not require the passage of a catheter. These typically have a straight distal end and a gauge size on the order of 21-22 gauge (iso-9626); while those of the latter type, through which a catheter is introduced, of necessity are somewhat larger, having a gauge size typically on the order of 17-18 gauge (iso-9626). The needles of the latter type, used for introducing a catheter into the epidural space, are described as possessing a curved tip so that the distal end of the catheter can curve upward for proper placement within the epidural space rather than perpendicularly abutting the dura mater, the delicate membrane lying over the arachnoid and pia mater covering the spinal cord.
U.S. Pat. No. 6,626,902 (Kucharczyk et al.) describes new hardware for delivery of drugs intraparenchymally and to regions of the brain in particular comprising a multi-lumen, multi-functional catheter system. The system comprises a plurality of axial lumens, at least one lumen supporting material delivery of primary treatment chemistry to a point of release and a second lumen having a component supporting a functionality electrostatically near the point of release other than material delivery and material removal wherein at least one biological or physiological measuring device is present within at least one lumen in which information from said at least one biological or physiological measuring device is connected to a host computer and said information is received by said host computer, wherein the component provides information other than information from said at least one biological or physiological measuring device and the component is connected to a host computer and said information is received by said host computer.
U.S. Pat. No. 6,537,232 (Kucharczyk et al.) describes a device and method for monitoring intracranial pressure during magnetic resonance (MR) image-guided neurosurgical procedures, such as intracranial drug delivery procedures, wherein an MR-compatible microsensor pressure transducer coupled to a pressure sensing diaphragm located a) at the tip, b) on a lateral side, and/or c) in multiple locations of an MR-compatible catheter is inserted into a lateral cerebral ventricle, cerebral cistern, subarachnoid space, subdural or extradural spaces, venous sinuses, or intraparenchymal tissue locations under MR imaging guidance, and is used to record intracranial pressures over hours to days in patients undergoing diagnostic or therapeutic neurologic interventions.
“Reflux-free cannula for convection-enhanced high speed delivery of therapeutic agents” by Michal T. Krauze et. al. Journal of Neurosurgery, vol. 103, pp 923-929, 2005 describes a two-lumen design called a step cannula in which a thin cannula projects of a larger lumen. The design is claimed to prevent backflow (see description of irreducible backflow below).
The standard current procedure for drug treatment of various focal neurological disorders, neurovascular diseases, and neurodegenerative processes requires neurosurgeons or interventional neuroradiologists to deliver drug agents by catheters or other tubular devices directed into the cerebrovascular or cerebroventricular circulation, or by direct injection of the drug agent, or cells which biosynthesize the drug agent, into targeted intracranial tissue locations. The blood-brain barrier and blood-cerebrospinal fluid barrier almost entirely exclude large molecules like proteins, and control entry of smaller molecules. Small molecules (<200 Daltons) which are lipid-soluble, not bound to plasma proteins, and minimally ionized, such as nicotine, ethanol, and some chemotherapeutic agents, readily enter the brain. Water soluble molecules cross the barriers poorly or not at all. Delivery of a drug into a ventricle bypasses the blood-brain barrier, and allows for a wide distribution of the drug in the brain ventricles, cisterns, and spaces due to the normal flow pathways of cerebrospinal fluid in the brain. However, following intracerebroventricular injection, many therapeutic drug agents, particularly large-molecular weight hydrophobic drugs, fail to reach their target receptors in brain parenchyma because of metabolic inactivation and inability to diffuse into brain tissues, which may be up to 18 mm from a cerebrospinal fluid surface.
To optimize a drug's therapeutic efficacy, it should be delivered to its target tissue at the appropriate concentration. A number of studies reported in the medical literature, for example, Schmitt, Neuroscience, 13, 1984, pp. 991-1001, have shown that numerous classes of biologically active drugs, such as peptides, biogenic amines, and enkephalins have specific receptor complexes localized at particular cell regions of the brain. Placing a drug delivery device directly into brain tissue thus has the notable advantage of initially localizing the injected drug within a specific brain region containing receptors for that drug agent. Targeted drug delivery directly into tissues also reduces drug dilution, metabolism and excretion, thereby significantly improving drug efficacy, while at the same time it minimizes systemic side-effects.
An important issue in targeted drug delivery is the accuracy of the navigational process used to direct the movement of the drug delivery device. Magnetic resonance imaging will likely play an increasingly important role in optimizing drug treatment of neurological disorders. One type of MR unit designed for image-guided therapy is arranged in a “double-donut” configuration, in which the imaging coil is split axially into two components. Imaging studies are performed with this system with the surgeon standing in the axial gap of the magnet and carrying out procedures on the patient. A second type of high-speed MR imaging system combines high-resolution MR imaging with conventional X-ray fluoroscopy and digital subtraction angiography (DSA) capability in a single hybrid unit. Both of these new generations of MR scanners provide frequently updated images of the anatomical structures of interest. This real-time imaging capability makes it possible to use high-speed MR imaging to direct the movement of catheters and other drug delivery vehicles to specific tissue locations, and thereby observe the effects of specific interventional procedures.
A prerequisite for MRI-guided drug delivery into the brain parenchyma, cerebral fluid compartments, or cerebral vasculature is the availability of suitable access devices. U.S. Pat. No. 5,571,089 to Crocker et al. and U.S. Pat. No. 5,514,092 to Forman et al. disclose endovascular drug delivery and dilatation drug delivery catheters which can simultaneously dilate and deliver medication to a vascular site of stenosis. U.S. Pat. No. 5,171,217 to March describes the delivery of several specific compounds through direct injection of microcapsules or microparticles using multiple-lumen catheters, such as disclosed by Wolinsky in U.S. Pat. No. 4,824,436. U.S. Pat. No. 5,580,575 to Unger et al. discloses a method of administering drugs using gas-filled liposomes comprising a therapeutic compound, and inducing the rupture of the liposomes with ultrasound energy. U.S. Pat. No. 5,017,566 to Bodor discloses redox chemical systems for brain-targeted drug delivery of various hormones, neurotransmitters, and drugs through the intact blood-brain barrier. U.S. Pat. No. 5,226,902 to Bae et al. and U.S. Pat. No. 4,973,304 to Graham et al. disclose drug delivery devices, in which biologically active materials present within a reversibly permeable hydrogel compartment can be delivered into tissues by various endogenous and exogenous stimuli. U.S. Pat. No. 5,167,625 to Jacobsen et al. discloses an implantable drug delivery system utilizing multiple drug compartments which are activated by an electrical circuit. U.S. Pat. No. 4,941,874 to Sandow et al. discloses a device for the injection of implants, including drug implants that may used in the treatment of diseases. U.S. Pat. Nos. 4,892,538, 4,892,538, 5,106,627, 5,487,739 and 5,607,418 to Aebischer et al. disclose implantable drug therapy systems for local delivery of drugs, cells and neurotransmitters into the brain, spinal cord, and other tissues using delivery devices with a semipermeable membrane disposed at the distal end. U.S. Pat. No. 5,120,322 to Davis et al. describes the process of coating the surface layer of a stent or shunt with lathyrogenic agent to inhibit scar formation during reparative tissue formation, thereby extending exposure to the drug agent. U.S. Pat. Nos. 4,807,620 to Strul and 5,087,256 to Taylor are examples of catheter-based devices which convert electromagnetic Rf energy to thermal energy. Technology practiced by STS Biopolymers (Henrietta, N.Y.) allows incorporation of pharmaceutical agents into thin surface coatings during or after product manufacture. The invention disclosed by STS Biopolymers allows for the drugs to diffuse out of the coating at a controlled rate, thereby maintaining therapeutic drug levels at the coating surface while minimizing systemic concentrations. The coating can incorporate natural or synthetic materials that act as antibiotics, anticancer agents, and antithrombotics, according to the issued patent. U.S. Pat. No. 5,573,668 to Grosh et al. discloses a microporous drug delivery membrane based on an extremely thin hydrophilic shell. U.S. Pat. No. 5,569,197 to Helmus et al. discloses a drug device guidewire formed as a hollow tube suitable for drug infusion in thrombolytic and other intraluminal procedures.
U.S. Pat. Nos. 6,026,316 and 6,061,587 (Kucharczyk et al.) advance the quality of delivery by enabling direct and even real-time observation of intraparenchymal drug delivery by non-invasive observational methods, even when delivery is itself invasive.
Published U.S. Patent Application No. 20030097116 (Putz, David A.) describes an improved assembly and method for accurately and safely delivering a drug to a selected intracranial site are disclosed. The assembly ensures delivery of the drug to the selected site by providing a barrier which prevents “backflow” or leakage of the drug. The assembly includes a guide catheter having an inflatable balloon which is able to seal or occlude the tract created by the insertion of the guide catheter into the brain. The guide catheter further includes a passageway which receives a delivery catheter through which the drug is administered to the selected site in the brain.
These advances within the field still allow for further advances in delivery methodologies that can improve or allow for alternative medical procedures for localized or distributed drug delivery within the brain. All references and Patents cited herein are incorporated herein by reference in their entirety.